The physiological mechanisms by which fever is produced in man and experimental animals have, for many years, intrigued medical practitioners and basic physiologists. Body tissue do not normally contain transferable fever-producing substances. If, however, phagocytic cells are activated by certain stimuli, they may synthesize pyrogenic factors of endogenous origin. First recognized about three decades ago, these endogenous substances were found to initiate the onset of fever if injected into a suitable assay animal. A variety of factors are produced and released from circulating leukocytes or tissue macrophages when these cells are stimulated either by pyrogenic substances or by engaging in phagocytic activity. Although initially called granulocytic or neutrophilic pyrogen, the fever-producing factors of cellular origin are now gennerally known as endogenous pyrogen, or EP. The entire field of body temperature regulation has been stimulated by the recent discovery that many cold-blooded animal species increase their internal body temperatures as a purposeful response to an experimental inoculation of pathogenic bacteria. Cold-blooded animals (and some infant mammals) increase their internal temperature by moving to a warmer environment. This form of behavioral fever is analagous to the development of clinical fever during the course of infectious or inflammatory processes in man. These exciting discoveries and the additional demonstrations that fever may be of benefit in terms of host survival have led to a renewed interest in fever and its underlying mechanisms. This interest is evidenced, in part, by the fact that the American Physiological Society has sponsored two recent symposia on this topic.